Composition comprising material for regulating OCT4 modification to repress stemness

Abstract

The present invention relates to a composition for repressing the sternness of stem cells, which comprises a material for regulating OCT4 modification. The material for regulating OCT4 modification according to the present invention may regulate the phosphorylation or methylation of OCT4 and inhibit Wnt signaling, thereby effectively reducing the sternness of various stem cells. Therefore, since it can be effectively used in inhibition of proliferation, recurrence and metastasis of cancer, and inhibition of resistance to an anticancer agent, and can reduce sternness even in normal stem cells, it is expected that the time for differentiation of embryonic stem cells into specific cells is shortened, and efficiency is increased.

The invention claimed is: 
     
       1. A method of inhibiting stemness of stem cells through regulation of OCT4 modification, comprising at least one selected from the group consisting of
 (a) administering a vector for transformation to a stem cell, the vector comprising genes encoding OCT4 phosphorylated at serine 281 in the amino acid sequence of mouse octamer-binding transcription factor 4 (OCT4) or serine 288 in the amino acid sequence of human OCT4; 
 (b) administering a vector for transformation to a stem cell, the vector comprising genes encoding OCT4 such that the methylation of arginine 179 in the amino acid sequence of mouse OCT4, arginine 186 in the amino acid sequence of human OCT4, lysine 215 in the amino acid sequence of mouse OCT4, or lysine 222 in the amino acid sequence of human OCT4 is inhibited; and 
 (c) administering a vector for transformation to a stem cell, the vector comprising genes encoding OCT4 such that the phosphorylation of serine 351 in the amino acid sequence of mouse OCT4 or serine 359 in the amino acid sequence of human OCT 4  is inhibited. 
 
     
     
       2. The method according to  claim 1 , further comprising:
 in (c), blocking activation of Wnt signaling. 
 
     
     
       3. The method according to  claim 1 , wherein the amino acid sequence of mouse OCT4 is represented by the amino acid sequence of SEQ ID NO: 1. 
     
     
       4. The method according to  claim 1 , wherein the amino acid sequence of human OCT4 is represented by the amino acid sequence of SEQ ID NO: 2. 
     
     
       5. The method according to  claim 1 , wherein the stem cells are selected from the group consisting of embryonic stem cells, gametes, cancer stem cells, and a combination thereof. 
     
     
       6. A method of screening a material for repressing the stemness of stem cells, the method comprising:
 (a) treating cells expressing mouse octamer-binding transcription factor 4 (OCT4) or human OCT4 with a candidate material or a vector for transformation, wherein the vector comprises at least one selected from the group consisting of: 
 genes encoding OCT4 phosphorylated at serine 281 in the amino acid sequence of mouse octamer-binding transcription factor 4 (OCT4) or serine 288 in the amino acid sequence of human OCT4; 
 genes encoding OCT4 such that the methylation of arginine 179 in the amino acid sequence of mouse OCT4, arginine 186 in the amino acid sequence of human OCT4, lysine 215 in the amino acid sequence of mouse OCT4, or lysine 222 in the amino acid sequence of human OCT4 is inhibited; and 
 genes encoding OCT4 such that the phosphorylation of serine 351 in the amino acid sequence of mouse OCT4 or serine 359 in the amino acid sequence of human OCT4 is inhibited; 
 (b) comparing at least one selected from the group consisting of the phosphorylation of serine 281 in the amino acid sequence of mouse OCT4 or serine 288 in the amino acid sequence of human OCT4, the methylation of arginine 179 in the amino acid sequence of mouse OCT4, arginine 186 in the amino acid sequence of human OCT4, lysine 215 in the amino acid sequence of mouse OCT4, or lysine 222 in the amino acid sequence of human OCT4, and the phosphorylation of serine 351 in the amino acid sequence of mouse OCT4 or serine 359 in the amino acid sequence of human OCT4 between the cells treated with the candidate material and the cells treated with the vector; and 
 (c) selecting the candidate material as a material for repressing the stemness of stem cells when serine 281 in the amino acid sequence of mouse OCT4 or serine 288 in the amino acid sequence of human OCT4 is phosphorylated, when the methylation of arginine 179 in the amino acid sequence of mouse OCT4, arginine 186 in the amino acid sequence of human OCT4, lysine 215 in the amino acid sequence of mouse OCT4, or lysine 222 in the amino acid sequence of human OCT4 is inhibited, or when the phosphorylation of serine 351 in the amino acid sequence of mouse OCT4 or serine 359 in the amino acid sequence of human OCT4 is inhibited. 
 
     
     
       7. The method according to  claim 6 , comprising:
 detecting whether Wnt signaling is activated in cells in (b); and 
 selecting the candidate material as a material for repressing the stemness of stem cells when the Wnt signaling is not activated in (c). 
 
     
     
       8. A method of diagnosing whether the stemness of stem cells is repressed, the method comprising:
 (a) comparing at least one selected from the group consisting of the phosphorylation of serine 281 in the amino acid sequence of mouse octamer-binding transcription factor 4 (OCT4) or serine 288 in the amino acid sequence of human OCT4, the methylation of arginine 179 in the amino acid sequence of mouse OCT4, arginine 186 in the amino acid sequence of human OCT4, lysine 215 in the amino acid sequence of mouse OCT4, or lysine 222 in the amino acid sequence of human OCT4, and the phosphorylation of serine 351 in the amino acid sequence of mouse OCT4 or serine 359 in the amino acid sequence of human OCT4 between cells expressing mouse OCT4 or human OCT4 and cells treated with a vector comprising at least one selected from the group consisting of: 
 genes encoding OCT4 phosphorylated at serine 281 in the amino acid sequence of mouse octamer-binding transcription factor 4 (OCT4) or serine 288 in the amino acid sequence of human OCT4; 
 genes encoding OCT4 such that the methylation of arginine 179 in the amino acid sequence of mouse OCT4, arginine 186 in the amino acid sequence of human OCT4, lysine 215 in the amino acid sequence of mouse OCT4, or lysine 222 in the amino acid sequence of human OCT4 is inhibited; and 
 genes encoding OCT4 such that the phosphorylation of serine 351 in the amino acid sequence of mouse OCT4 or serine 359 in the amino acid sequence of human OCT4 is inhibited; and 
 (b) determining that the stemness of stem cells is repressed when serine 281 in the amino acid sequence of mouse OCT4 or serine 288 in the amino acid sequence of human OCT4 is phosphorylated, when the methylation of arginine 179 in the amino acid sequence of mouse OCT4, arginine 186 in the amino acid sequence of human OCT4, lysine 215 in the amino acid sequence of mouse OCT4, or lysine 222 in the amino acid sequence of human OCT4 is inhibited, or when the phosphorylation of serine 351 in the amino acid sequence of mouse OCT4 or serine 359 in the amino acid sequence of human OCT4 is inhibited. 
 
     
     
       9. The method according to  claim 8 , comprising:
 confirming whether Wnt signaling is activated in cells expressing mouse OCT4 or human OCT4 in (a); and 
 determining that the stemness of stem cells is repressed when the Wnt signaling is not activated in (b).